Non-alcoholic SteatohepatitisPhase 2RestoreNCT03437720
Assessment of the Safety and Effect of SAR425899 Versus Placebo for the Treatment of Non-alcoholic Fatty Liver Disease
A Phase 2 study testing SAR425899 in people with Non-alcoholic Steatohepatitis and Type 2 Diabetes Mellitus, run by Sanofi.
Trial summary
Primary Objective: To evaluate the dose response relationship of SAR425899 compared to placebo on resolution of non-alcoholic steatohepatitis (NASH) with no worsening of fibrosis in diabetic and non-diabetic patients with histopathologically-confirmed NASH. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Non-alcoholic Steatohepatitis, Type 2 Diabetes Mellitus
- What is being tested?
- SAR425899
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 23 May 2019to 25 Aug 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Non-diabetic or type 2 diabetes mellitus with confirmed non-alcoholic steatohepatitis.
- Non-alcoholic fatty liver disease (NAFLD) activity score (NAS) >=4 with each of its components >=1.
- Patients without Type 2 diabetes determined by HbA1c (glycated hemoglobin) <6.5% and Fasting Plasma Glucose (FPG) <7.0 mmol/L (<126 mg/dL).
- Stable glycemic control (HbA1c <9.0%) and metabolic disorders managed with diet/exercise and/or stable dose metformin and/or sulphonylureas for at least 3 months prior to screening (type 2 diabetes patients).
- Signed written informed consent form.
Who cannot join
- Diagnosis of type 1 diabetes mellitus.
- Previous insulin use or use of insulin within the last 6 months, except for episode(s) of short-term treatment (<15 consecutive days) due to intercurrent illness.
- Body Mass Index (BMI) <25 kg/m2 or >45.0 kg/m2.
- Current participation in organized diet/weight reduction program or clinical trial of weight control (within the last 3 months prior to screening), or weight loss attempt, plans for major changes in physical activities or significant change in body weight in the 2 months prior to screening (significant change in body weight is defined as >=5% self-reported change within 6 months prior to randomization if a pre-existing liver biopsy sample was collected prior to screening period.
- Current treatment with glucose-lowering agent(s) other than metformin or sulphonylureas, weight loss drugs including orlistat, systemic steroids, methotrexate, amiodarone, or Vitamin E.
- Alcoholism (past or present) and/or average alcohol consumption per week >21 units (210 g) for males, >14 units (140 g) for females within the last 5 years.
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- Poorly controlled hypertension (resting systolic blood pressure (SBP) >160 mm Hg and/or resting diastolic blood pressure (DBP) >95 mm Hg) at screening.
- Some liver diseases, pancreatic disease, liver transplantation and types of cancer.
- Pregnant or breast-feeding women.
- Women of childbearing potential (WOCBP) not protected by highly-effective method(s) of birth control and/or who are unwilling or unable to be tested for pregnancy.
- Male subjects, whose partners are able to become pregnant, who do not accept to use a condom during sexual intercourse from study inclusion up to 3 months after last dosing; or who are planning to donate sperm from study inclusion up to 3 months after last dosing.
- Patients with coronary, carotid, or peripheral artery revascularization procedures planned during the screening or treatment phases of the protocol.
- Patients with unstable heart conditions.
- The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
About this study
Official title: A 52-week Double-blind, Randomized, Placebo-controlled, Phase 2 Study to Assess the Efficacy and Safety of SAR425899 for the Treatment of Non-alcoholic Steatohepatitis (NASH)
Primary Objective:
- To evaluate the dose response relationship of SAR425899 compared to placebo on resolution of non-alcoholic steatohepatitis (NASH) with no worsening of fibrosis in diabetic and non-diabetic patients with histopathologically-confirmed NASH.
Read more
Secondary Objectives:
- To assess the effect of SAR425899 on overall non-alcoholic fatty liver disease (NAFLD) activity score (NAS), individual components of NAS (steatosis, hepatocyte ballooning, and lobular inflammation), and fibrosis score.
- To assess to the effect of SAR425899 on MRI-PDFF (Magnetic Resonance Imaging-determined Proton Density Fat Fraction) derived parameters (total liver fat, liver volume, and fractional liver fat content).
- To assess the effect of SAR425889 on body weight and waist/hip circumference ratio.
- To assess SAR425899 pharmacokinetics.
- To assess safety and tolerability of SAR425899.
Read the detailed description
Study duration per participant will be approximately 64 weeks, consisting of up to 8 weeks screening plus 52 weeks treatment and 4 weeks post treatment follow-up.
- Being tested
- SAR425899, Placebo
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SAR425899Drug
Pharmaceutical form: Solution for injection
Route of administration: Subcutaneous injection
PlaceboDrug
Pharmaceutical form: Solution for injection
Route of administration: Subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| SAR425899 (Low Dose) | Experimental | Once daily dose with weekly dose escalations, if tolerated, until target dose is reached. From week 14 (Day 99) until week 52, no further dose adjustments are planned. Receives: Drug: SAR425899 |
| SAR425899 (High Dose) | Experimental | Once daily dose with weekly dose escalations, if tolerated, until target dose is reached. From week 14 (Day 99) until week 52, no further dose adjustments are planned. Receives: Drug: SAR425899 |
| Placebo (Low Dose) | Placebo comparator | Once daily dose with weekly dose escalations, if tolerated, until target dose is reached. From week 14 (Day 99) until week 52, no further dose adjustments are planned. Receives: Drug: Placebo |
| Placebo (High Dose) | Placebo comparator | Once daily dose with weekly dose escalations, if tolerated, until target dose is reached. From week 14 (Day 99) until week 52, no further dose adjustments are planned. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Resolution of Non-alcoholic steatohepatitis (NASH)
Percentage of participants with absence of hepatocyte ballooning (NAFLD - non-alcoholic fatty liver disease - activity score, NAS = 0) without worsening of fibrosis score at week 52. -
Measured: Week 52
Secondary outcomes (16)
No hepatocyte ballooning, lobular inflammation score 0 or 1, without worsening of fibrosis
Percentage of participants with absence of hepatocyte ballooning (NAS = 0), lobular inflammation NAS = 0 or 1, without worsening of fibrosis score at week 52.
Measured: Week 52
Change in overall NAFLD activity score (NAS)
Change from baseline to week 52 in overall NAFLD activity score (NAS).
Measured: Baseline to week 52
Change in NAS individual components
Change from baseline to week 52 in individual components of NAS (steatosis).
Measured: Baseline to week 52
Change in NAS individual components
Change from baseline to week 52 in individual components of NAS (hepatocyte ballooning).
Measured: Baseline to week 52
Change in NAS individual components
Change from baseline to week 52 in individual components of NAS (lobular inflammation).
Measured: Baseline to week 52
Change in fibrosis score
Change from baseline to week 52 in fibrosis score.
Measured: Baseline to week 52
Major adverse cardiac events
Number of patients with major cardiac events
Measured: Baseline to week 52
Change in Magnetic Resonance Imaging-determined Proton Density Fat Fraction (MRI-PDFF)
Change from baseline to week 26 and to week 52 in MRI-PDFF-derived total liver fat, liver volume and fractional liver fat content.
Measured: Baseline to week 26 and week 52
Improvement of fibrosis without worsening of hepatocyte ballooning component of NAS
Percentage of participants with improvement of fibrosis by at least 1 stage without worsening of hepatocyte ballooning component of NAS at week 52
Measured: Week 52
Change in body weight
Change from baseline to week 52 in body weight
Measured: Baseline to week 52
Change in waist circumference
Change from baseline to week 52 in waist circumference
Measured: Baseline to week 52
Change in hip circumference
Change from baseline to week 52 in hip circumference
Measured: Baseline to week 52
Change in waist to hip ratio
Change from baseline to week 52 in waist to hip ratio
Measured: Baseline to week 52
Assessment of pharmacokinetic (PK) parameter: AUC0-24
Area under the concentration-time curve from 0 to 24 hours (AUC0-24)
Measured: Week 52
Assessment of PK parameter: Cmax
Observed maximum plasma concentration after administration (Cmax)
Measured: Week 52
Assessment of PK parameter: Ctrough
Plasma concentration immediately prior to treatment administration during repeat dosing levels (Ctrough)
Measured: Baseline to week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study start23 May 2019 (estimated)
- Primary completion25 Aug 2021 (estimated)
- Study completion25 Aug 2021 (estimated)
Why it stopped: Sponsor decision to cancel TRIAL, not related to safety concern.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-alcoholic SteatohepatitisStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03437720
- Sponsor's protocol ID
- ACT15067
- Other IDs
- 2017-002371-26, U1111-1191-5486, 2017
- Acronym
- Restore
- Status last verified
- Apr 2022
- First submitted
- 13 Feb 2018
- Last updated
- 13 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 52-week Double-blind, Randomized, Placebo-controlled, Phase 2 Study to Assess the Efficacy and Safety of SAR425899 for the Treatment of Non-alcoholic Steatohepatitis (NASH)
- ClinicalTrials.gov ID
- NCT03437720
- Acronym / sponsor ID
- Restore / ACT15067
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor decision to cancel TRIAL, not related to safety concern.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- 23 May 2019 (estimated)
- Primary completion
- 25 Aug 2021 (estimated)
- Study completion
- 25 Aug 2021 (estimated)
- First posted
- 19 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
- To evaluate the dose response relationship of SAR425899 compared to placebo on resolution of non-alcoholic steatohepatitis (NASH) with no worsening of fibrosis in diabetic and non-diabetic patients with histopathologically-confirmed NASH.
Secondary Objectives:
- To assess the effect of SAR425899 on overall non-alcoholic fatty liver disease (NAFLD) activity score (NAS), individual components of NAS (steatosis, hepatocyte ballooning, and lobular inflammation), and fibrosis score.
- To assess to the effect of SAR425899 on MRI-PDFF (Magnetic Resonance Imaging-determined Proton Density Fat Fraction) derived parameters (total liver fat, liver volume, and fractional liver fat content).
- To assess the effect of SAR425889 on body weight and waist/hip circumference ratio.
- To assess SAR425899 pharmacokinetics.
- To assess safety and tolerability of SAR425899.
Detailed description
Study duration per participant will be approximately 64 weeks, consisting of up to 8 weeks screening plus 52 weeks treatment and 4 weeks post treatment follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| SAR425899 (Low Dose) | Experimental | Drug: SAR425899Once daily dose with weekly dose escalations, if tolerated, until target dose is reached. From week 14 (Day 99) until week 52, no further dose adjustments are planned. |
| SAR425899 (High Dose) | Experimental | Drug: SAR425899Once daily dose with weekly dose escalations, if tolerated, until target dose is reached. From week 14 (Day 99) until week 52, no further dose adjustments are planned. |
| Placebo (Low Dose) | Placebo comparator | Drug: PlaceboOnce daily dose with weekly dose escalations, if tolerated, until target dose is reached. From week 14 (Day 99) until week 52, no further dose adjustments are planned. |
| Placebo (High Dose) | Placebo comparator | Drug: PlaceboOnce daily dose with weekly dose escalations, if tolerated, until target dose is reached. From week 14 (Day 99) until week 52, no further dose adjustments are planned. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Non-diabetic or type 2 diabetes mellitus with confirmed non-alcoholic steatohepatitis.
- Non-alcoholic fatty liver disease (NAFLD) activity score (NAS) >=4 with each of its components >=1.
- Patients without Type 2 diabetes determined by HbA1c (glycated hemoglobin) <6.5% and Fasting Plasma Glucose (FPG) <7.0 mmol/L (<126 mg/dL).
- Stable glycemic control (HbA1c <9.0%) and metabolic disorders managed with diet/exercise and/or stable dose metformin and/or sulphonylureas for at least 3 months prior to screening (type 2 diabetes patients).
- Signed written informed consent form.
Key exclusion criteria (14 listed)
- Diagnosis of type 1 diabetes mellitus.
- Previous insulin use or use of insulin within the last 6 months, except for episode(s) of short-term treatment (<15 consecutive days) due to intercurrent illness.
- Body Mass Index (BMI) <25 kg/m2 or >45.0 kg/m2.
- Current participation in organized diet/weight reduction program or clinical trial of weight control (within the last 3 months prior to screening), or weight loss attempt, plans for major changes in physical activities or significant change in body weight in the 2 months prior to screening (significant change in body weight is defined as >=5% self-reported change within 6 months prior to randomization if a pre-existing liver biopsy sample was collected prior to screening period.
- Current treatment with glucose-lowering agent(s) other than metformin or sulphonylureas, weight loss drugs including orlistat, systemic steroids, methotrexate, amiodarone, or Vitamin E.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SAR425899Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection | Drug | SAR425899 (High Dose), SAR425899 (Low Dose) |
| PlaceboPharmaceutical form: Solution for injection Route of administration: Subcutaneous injection | Drug | Placebo (High Dose), Placebo (Low Dose) |
Primary outcome
Resolution of Non-alcoholic steatohepatitis (NASH)
Time frame: Week 52
Percentage of participants with absence of hepatocyte ballooning (NAFLD - non-alcoholic fatty liver disease - activity score, NAS = 0) without worsening of fibrosis score at week 52. -
16 secondary outcomes
No hepatocyte ballooning, lobular inflammation score 0 or 1, without worsening of fibrosis
Time frame: Week 52
Change in overall NAFLD activity score (NAS)
Time frame: Baseline to week 52
Change in NAS individual components
Time frame: Baseline to week 52
Change in NAS individual components
Time frame: Baseline to week 52
Change in NAS individual components
Time frame: Baseline to week 52
Change in fibrosis score
Time frame: Baseline to week 52
Major adverse cardiac events
Time frame: Baseline to week 52
Change in Magnetic Resonance Imaging-determined Proton Density Fat Fraction (MRI-PDFF)
Time frame: Baseline to week 26 and week 52
Improvement of fibrosis without worsening of hepatocyte ballooning component of NAS
Time frame: Week 52
Change in body weight
Time frame: Baseline to week 52
Change in waist circumference
Time frame: Baseline to week 52
Change in hip circumference
Time frame: Baseline to week 52
Change in waist to hip ratio
Time frame: Baseline to week 52
Assessment of pharmacokinetic (PK) parameter: AUC0-24
Time frame: Week 52
Assessment of PK parameter: Cmax
Time frame: Week 52
Assessment of PK parameter: Ctrough
Time frame: Baseline to week 52
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2022.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SAR425899 in people with Non-alcoholic Steatohepatitis and Type 2 Diabetes Mellitus, run by Sanofi.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 13 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Resolution of Non-alcoholic steatohepatitis (NASH) (time frame: Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2022.